This is a Mid-Career Investigator (K 24) proposal for Ellen Seely, MD. The goal of this proposal is threefold. First, it would increase the depth of Dr. Seely's research by enabling the investigator to receive further advanced training in human genetics. Second, it would give the investigator the supported time to formally train young investigators in patient-oriented research in the field of hormonal control of blood pressure. Third, it would allow the investigator to use her experience as Associate Program Director of the General Clinical Research Center (GCRC) to teach the next generation of patient-oriented researchers about the use of a GCRC for the study of human pathophysiology using varied GCRC-based investigative techniques. Dr. Seely's research topic "Blood Pressure in Postmenopausal Women: a GCRC Study" serves as fertile ground for a K24. Hypertension affects over 20 million women in the United States and the majority of these women are postmenopausal. Although there is clearly a genetic component to hypertension in both men and women, its incidence increases dramatically in women following menopause superceding that in men and suggests that the hormonal milieu of the premenopausal state may be protective against the manifestation of hypertension. The overall goal of Dr. Seely's research plan is to utilize the GCRC for detailed studies of the pathophysiology of hypertension in postmenopausal women. Dr. Seely plans to determine how polymorphisms of genes of the renin-angiotensin-aldosterone system (RAAS), a major regulator of blood pressure, are influenced by estradiol. An understanding of the interaction of estradiol with specific polymorphisms of the RAAS that lead to blood pressure lowering may enable the development of selective estrogen receptor modulators that have antihypertensive effects. Thus, funding of this proposal will allow Dr. Seely to expand her own research career and simultaneously provide time to expand her mentorship role.